Received a not approvable letter 7/08

Began pivotal Phase III trial to test product as adjunct therapy with acetyl cholinesterase inhibitors in about 1,100 patients with mild to moderate AD 10/05; Phase III trials ended in order to get an earlier look at potential efficacy 10/06; Phase III trial turned up positive outcome trends among women, but no positive effect among men 5/07

Began pivotal Phase III trial 11/04; suspended dosing due to liver enzyme elevations 8/05

Began pivotal Phase III trial, for pain following bunionectomy surgery, under FDA SPA 9/04; began third, in lower back pain, of seven planned Phase IIIs 12/04; began Phase III in patients following hysterectomy 8/05; Phase III trial for pain following bunionectomy surgery showed statistical significance 9/05; a positive futility analysis was made after first 300 patients in pivotal Phase III trial in lower back pain, so trial will continue to completion 12/05; Phase III trial in 600 patients

Failed to significantly reduce postoperative pain over placebo in a pivotal study 1/08; Phase III trial showed it was well tolerated and provided significantly better pain relief than placebo following orthopedic surgery; a separate study showed a statistically significant reduction of fever 7/08; data showed that the 1000 mg dose significantly reduced pain intensity over 24 hours 12/08

More than 133 patients have enrolled in a pivotal Phase III study 11/07; independent data safety monitoring board has reviewed data from the ongoing U.S. pivotal Phase III trial and recommended it continue 12/07; an independent data safety monitoring board recommended the Phase III trial continue 4/08; completed patient recruitment in its Phase III trial 8/08

The dose-escalating portion of a chronic toxicology study demonstrated it is safe and well tolerated; company plans to begin Phase III enrollment 2/07; NIH started a Phase III trial with more than 1,720 patients 3/07

Phase III trial failed to show statistical significance on primary or secondary endpoints, though a trend of decreased mortality was seen 5/06

FDA issued an approvable letter that calls for additional safety and efficacy data 10/06

Trial in PBA patients with multiple sclerosis showed statistically significant benefit 8/04; completed rolling NDA submission 7/05; FDA wants more info 9/05; FDA accepted NDA filing and granted it priority review 4/06; FDA extended its review period, and Oct. 30 is the new PDUFA date 6/06; completed targeted enrollment of patients into the STAR trial, a confirmatory Phase III trial 3/09

Phase III data indicated Zingo reduced pain in adult patients 10/07; submitted a supplemental NDA to expand Zingo's use 3/08; Phase III data showed significantly less pain during line placement or venipuncture as compared to placebo 5/08

Outlined Phase II/III program and expects to start trials this year 1/07; started a pivotal Phase III trial in 300 patients 3/08; missed its primary end-point of reducing pain, but hit a secondary endpoint of reducing opioid use 11/08; data showed it significantly reduced post-surgery pain up to 48 hours following total knee replacement 12/08

Met primary endpoint in Phase III, missed secondary endpoints 10/02; gene-variant analysis showed potential from failed Phase III 8/04; began Phase III trial 6/05; began two pivotal Phase III trials under SPA with FDA 9/05; drug failed to hit primary and secondary endpoints in two Phase III studies 4/07

Phase III trial results positive 9/06; opened 7 sites for the first stage of its Phase III trial 4/08

Phase III data showed it demonstrated significant pain relief, meeting the primary endpoint 11/07; submitted an NDA 2/08; withdrew its NDA and plans to submit a revised application 4/08; FDA accepted and designated for priority review the NDA 9/08

Met the primary endpoint of reducing agitation in a Phase III trial with 5-mg and 10-mg doses 9/08

Phase III data showed a decrease in number of headache days that was significantly greater than placebo 9/08

Initiated a Phase III trial 6/08; received approval from the Russian regulatory authorities 8/08

Phase III trial in 574 pediatric patients demonstrated statistically significant less pain for drug group vs. placebo 10/05; Phase III trial in 535 pediatric patients getting venipunctures and intravenous line placements demonstrated statistically significant pain relief vs. placebo 11/05